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[Effect of cyclophosphamide in experimental histoplasmosis in the rat]
J G Gago1, C M Godio, L B Ochoa
1Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Abstract:
Histoplasmosis is a fungal disease caused by the dimorphous fungus Histoplasma capsulatum (Hc). Cyclophosphamide (Cy) was used as an immunomodulator capable of modifying the course of the disease, as well as of regulating the mechanisms involved in T-lymphocyte mediated immune response. Rats were subjected to intracardiac inoculation of Hc followed by a fractionated treatment with a 100 mg/kg body weight dose of Cy on days +4, +5, +6, +7 and +11 pi. Until day 26 pi, treatment with Cy caused 85% mortality whereas no mortality was observed among animals only inoculated with Hc. On day 14 pi, the group of Hc animals showed a delayed hypersensitivity test (DH) of 26.60 + 13.96 as determined by the swelling of the leg. Conversely, DH was significantly depressed in rats inoculated with Hc and treated with Cy: 3.88 +/- 1.00 (p < 0.01). Colony forming units count in this group was 2020 CFU/g of spleen, and 24 CFU/g of spleen (p < 0.01) in controls. A macroscopic study of the organs revealed that the animals in the Hc+Cy group had spleenomegaly and lungs with granuloma and hemorrhagic spots. The controls only presented small lung abscesses. These findings lead to the conclusion that Cy causes a deterioration of cell mediated immune response which results in the manifestation of an acute, fatal experimental mycosis.
Insights
Cyclophosphamide (Cy) treatment worsened experimental Histoplasmosis in rats, increasing mortality and fungal burden by impairing cell-mediated immunity. This highlights Cy
Area of Science:
- Mycology: Investigating Histoplasma capsulatum, a dimorphic fungus responsible for histoplasmosis.
- Immunology: Examining the role of T-lymphocyte mediated immune responses in fungal infections.
- Pharmacology: Assessing the immunomodulatory effects of cyclophosphamide (Cy) on experimental mycosis.
Context:
- Histoplasmosis is a significant fungal disease.
- Cyclophosphamide (Cy) is known to modulate immune responses.
- Understanding the interplay between immunosuppression and fungal infections is crucial.
Purpose:
- To investigate the effect of cyclophosphamide (Cy) on experimental Histoplasmosis in rats.
- To evaluate the impact of Cy on cell-mediated immunity during Hc infection.
- To determine the mortality rates and organ pathology in Cy-treated Hc-infected rats.
Summary:
- Rats infected with Histoplasma capsulatum (Hc) and treated with cyclophosphamide (Cy) exhibited 85% mortality by day 26, compared to no mortality in controls.
- Cy treatment significantly suppressed delayed hypersensitivity (DH) response and increased fungal burden (2020 CFU/g spleen) in Hc-infected rats.
- Macroscopic examination revealed spleenomegaly, lung granulomas, and hemorrhagic spots in Hc+Cy group, indicating severe disease progression.
Impact:
- Cyclophosphamide (Cy) exacerbates experimental Histoplasmosis by deteriorating cell-mediated immunity.
- This study demonstrates that Cy treatment leads to an acute and fatal outcome in this experimental mycosis model.
- Findings underscore the critical role of intact cell-mediated immunity in controlling Histoplasma capsulatum infections.